Peptidoglycan associated cyclic lipopeptide disrupts viral infectivity

Abstract

1Enteric viruses exploit bacterial components including lipopolysaccharides (LPS) and 2 peptidoglycan (PG) to facilitate infection in humans. With origins in the bat enteric system, we 3 wondered if severe acute respiratory syndrome-coronavirus (SARS-CoV) or Middle East 4 respiratory syndrome-CoV (MERS-CoV) also use bacterial components to modulate infectivity. 5To test this question, we incubated CoVs with LPS and PG and evaluated infectivity finding no 6 change following LPS treatment. However, PG from B. subtilis reduced infection >10,000-fold 7 while PG from other bacterial species failed to recapitulate this. Treatment with an alcohol 8 solvent transferred inhibitory activity to the wash and mass spectrometry revealed surfactin, a 9 cyclic lipopeptide antibiotic, as the inhibitory compound. This antibiotic had robust dose-and 1 0 temperature-dependent inhibition of CoV infectivity. Mechanistic studies indicated that surfactin 1 1 disrupts CoV virion integrity and surfactin treatment of the virus inoculum ablated infection in 1 2 vivo. Finally, similar cyclic lipopeptides had no effect on CoV infectivity and the inhibitory effect

SARS‐CoV‐2 spike glycoprotein‐binding proteins expressed by upper respiratory tract bacteria may prevent severe viral infection

“…As discussed above, there is emerging evidence suggesting suppression of influenza virus infection by bacteria. Additionally, it is shown that a peptidoglycan produced by the Gram‐positive bacterium Bacillus subtilis, a member of phylum Firmicutes, can abrogate infectivity of SARS‐CoV and Middle Eastern respiratory syndrome coronavirus (MERS‐CoV) [30]. Thus, although the interaction of SARS‐CoV‐2 and URT commensal microbiota should yet be investigated, it is reasonable to assume such an interaction plays a role in pathogenesis of the virus.…”

Novel ionophores active against La Crosse virus identified through rapid antiviral screening

“…Because we observe significant reductions in LACV titers with valinomycin treatment, we hypothesized that valinomycin might be directly affecting cellular processes to reduce virus infection. Nonetheless, valinomycin is a cyclic peptide and could potentially directly inactivate viral particles, as seen previously 20 . To test whether valinomycin directly reduced virus infectivity, we directly incubated LACV with 2 µM valinomycin for 24h and directly titered the surviving virus at regular intervals.…”

“…ZIKV, LACV, and, KEYV were obtained from Biodefense and Emerging Infections (BEI) Research Resources. HCoV-229E and MERS-CoV were propagated and quantitated via standard methods as previously described 20 .For all infections, drug was maintained throughout infection as designated. Viral stocks were maintained at −80°C.…”

Is a healthy microbiome responsible for lower mortality in COVID-19?

“…Therefore, it is also effective against many other viruses, such as influenza A (strains H1N1 and H3N2), Ebola and Zika. The usage of B. subtilis peptidoglycans reduces infectivity of CoV viruses (Johnson et al 2019 ). In China, Bacillus subtilis , Bacillus licheniformis and Bacillus cereus are ingested by adults, infants and newborns to relieve diarrhoea and build healthy intestinal microbiota.…”